ArticleStem cell research & therapy2021
LINGO-1 regulates Wnt5a signaling during neural stem and progenitor cell differentiation by modulating miR-15b-3p levels.
Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- M1-BMDMs with Wnt5a deletion attenuate liver fibrosis by suppression of Wnt5a/Frizzled 2 axis in hepatic progenitors.Cell & bioscience · 2025Article
- Effects of subanesthetic dose of ketamine on motor and cognitive outcomes of harmaline-induced essential tremor model: a focus on Lingo-1 and inflammatory pathways.BMC neuroscience · 2025Article
- Review
- Transplantation of Wnt5a-modified Bone Marrow Mesenchymal Stem Cells Promotes Recovery After Spinal Cord Injury via the PI3K/AKT Pathway.Molecular neurobiology · 2024Article
- Therapeutic effects of exendin-4 on spinal cord injury via restoring autophagy function and decreasing necroptosis in neuron.CNS neuroscience & therapeutics · 2024Article
- Highly Accurate Estimation of Cell Type Abundance in Bulk Tissues Based on Single-Cell Reference and Domain Adaptive Matching.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Wnt signaling pathway in spinal cord injury: from mechanisms to potential applications.Frontiers in molecular neuroscience · 2024Review
- Recent progress and challenges in the treatment of spinal cord injury.Protein & cell · 2023Review
- Non-Coding RNAs in the Regulation of Hippocampal Neurogenesis and Potential Treatment Targets for Related Disorders.Biomolecules · 2022Review
- Current status of neural progenitor/stem cells for spinal cord injury: fundamental research and clinical trials.Frontiers in neurologyReview
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundManipulation of neural stem and progenitor cells (NSPCs) is critical for the successful treatment of spinal cord injury (SCI) by NSPC transplantation, since their differentiation into neurons and oligodendrocytes can be inhibited by factors present in inflamed myelin. In this study, we examined the effects of LINGO-1 on spinal cord-derived NSPC (sp-NSPC) differentiation, the underlying mechanisms of action, and the functional recovery of mice after transplantation of manipulated cells.
methodssp-NSPCs were harvested from female adult C57/BL6 mice after SCI induced with an NYU impactor. These cells were infected with lentiviral vectors containing LINGO-1 shRNA sequence or a scrambled control and transplanted into SCI mice. Tuj-1- and GFAP-positive cells were assessed by immunofluorescence staining. Wnt5a, p-JNK, JNK, and β-catenin expression was determined by Western blot and RT-qPCR. miRNAs were sequenced to detect changes in miRNA expression. Motor function was evaluated 0-35 days post-surgery by means of the Basso Mouse Scale (BMS) and by the rotarod performance test.
resultsWe discovered that LINGO-1 shRNA increased neuronal differentiation of sp-NSPCs while decreasing astrocyte differentiation. These effects were accompanied by elevated Wnt5a protein expression, but unexpectedly, no changes in Wnt5a mRNA levels. miRNA-sequence analysis demonstrated that miR-15b-3p was a downstream mediator of LINGO-1 which suppressed Wnt5a expression. Transplantation of LINGO-1 shRNA-treated sp-NSPCs into SCI mice promoted neural differentiation, wound compaction, and motor function recovery.
conclusionsLINGO-1 shRNA promotes neural differentiation of sp-NSPCs and Wnt5a expression, probably by downregulating miR-15b-3p. Transplantation of LINGO-1 shRNA-treated NSPCs promotes recovery of motor function after SCI, highlighting its potential as a target for SCI treatment.
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